Method and apparatus for monitoring and/or controlling the neuromuscular blocking, specially the blocking produced by muscular relaxing pharmaceuticals during anaesthesia

ABSTRACT

The method consists in the stimulation of a nerve and the detection and measurement of the response and is characterized in that the nerve stimulation is done in the skin which covers the muscles on which the detection of the response is performed. 
     The apparatus comprises means for the application of the nerve stimulation, means for the detection of the response and, optionally, means for the monitoring of the neuromuscular block, and it is characterized in that said means are provided in a single body, which is a cuff of the type used for measuring arterial pressure, provided with means for a detection of pressure or connected to said means. 
     It is not necessary to stimulate any peripheral nerves, and the apparatus is more compact and handy.

The present invention pertains to a device for the monitoring and/orcontrolling of the neuromuscular block, especially that produced bymuscle relaxant drugs used during anaesthesia.

Primarily, the new method and apparatus allow a quantification andcontrol of the neuromuscular block by means of transcutaneousstimulation directly on the muscle, stimulating the intramuscular nervepathways and the neural part of the motor plate without the need ofhaving to stimulate a peripheral motor nerve.

The invention also allows a controlled administration of the blockerdrug during the induction of the anaesthesia, as well as control of theneuromuscular block during the operation and control of the recoverywhen being awakened from the anaesthesia.

ANTECEDENTS OF THE INVENTION

It is known that major advances in surgery have come about from theapplication of muscle relaxant drugs during anaesthesia, which inaddition to facilitating the work of the surgeon also allows a lesstraumatic intubation and facilitates mechanical respiration.

Likewise, muscle relaxation allows improved mechanical ventilation forintubated patients at intensive care wards.

It is also known that there are various factors which influence theduration and effect of the muscle relaxants, depending among otherthings on the body weight, the age, the physical condition and possiblepathologies of the patient to whom this type of drug is beingadministered. In the event that the dose is insufficient, the intubationand the subsequent surgery might become more difficult; in the case ofoverdosage, the patient upon awakening from the anaesthesia mightpresent respiratory insufficiency and a need for prolonged artificialrespiration, which would delay their leaving the operating theater ortheir admission to a special care ward.

Other dangers of overdosage or poor reversal of the effects of musclerelaxants might be serious complications such as aspiration of vomit onaccount of faulty reflexes or respiratory failure, which complicationsmay eventually cause the death of the patient.

In order to avoid these complications, at present, the status of theneuromuscular block is evaluated by means of stimulation of a peripheralmotor nerve and measurement of the degree of motility of the muscleinnervated by said nerve.

There are various methods and devices designed to stimulate peripheralnerves by means of transcutaneous electrodes, for example, thestimulators of Neuro Technology, Inc., Houston, Tex., U.S.A. The mostimportant problem lies in the evaluation or measurement and monitoringof the neuromuscular block and the adequate administration of the musclerelaxant drug to maintain the desired level of blockage. At present, theevaluation of the block is done by evaluation of the electricalactivity, the force or the movement of the muscle during itscontraction. The methods used up to the present date are:

1) The visual method. One visually evaluates the movement of a muscleafter the stimulation of the motor nerve which innervates it. Theinexactitude and difficulty of quantification of the method are obvious,but its simplicity makes it the one which is used most frequently today.

2) The tactile method. Similar to the preceding method, but in this casethe evaluation is done by means of the perception through the hand ofthe anesthesiologist of the force of contraction of the patient afterthe stimulus. As in the preceding case, it is a subjective and inexactmethod, offering little guarantee of determining the exact degree ofneuromuscular blockage.

3) By means of electromyography. This consists in the registration ofthe muscular electrical activity evoked by stimulating the motor nervewhich innervates said muscle. There are various devices and apparatus onthe market, which monitor the neuromuscular block by said technique,which is described, for example, in U.S. Pat. No. 4,291,705, amongothers. The primary problem which this technique entails is itsdifficulty of application and the sophistication of the equipment, sothat it has only been used essentially in research, without coming to beused as a practical and routine technique.

4) By means of force transducers. In this case, one registers the forceof the thumb when the ulnar nerve is stimulated. Again, there arevarious devices on the market, such as the "Relaxograph" of BiometerInternational A/S, Denmark. As in the preceding case, the primaryproblem consists in the complexity of the technique used, which involveshaving to immobilize the arm in order to perform a proper registration.For this reason, and the costly equipment, this device is not verypractical for routine use.

5) By means of accelerometry. This method is, after the visual method,the most popular one. It is based on placing a biaxial or biaxialaccelerometric sensor on the thumb which, when the ulnar nerve isstimulated, provokes a movement in same, which is picked up by theaccelerometer. This is a rather valid method, but it still has thedrawback that several electrodes separate from the sensor have to be putin place in order to stimulate the peripheral nerve. On the other hand,the accelerometer is fragile and requires a certain immobilization ofthe arm. Other placements of the accelerometer have been described, forexample, on the face, in which case one must stimulate a motor branch ofthe facial nerve and the stimulus electrodes must arrive separately fromthe accelerometer, increasing the risk of certain of the elementsbecoming detached from the skin. As an example of monitors based onaccelerometry, one can mention the "Accelograph" and "Tof-Guard" models,both of them from Biometer International A/S, Denmark, and thatdescribed in U.S. Pat. No. 4,817,628, which is another example of afacial accelerometer.

6) By means of flexible-sheet piezoelectric sensors. The phenomenon ofpiezoelectricity has been known for many years, as has been itsapplication in the field of medicine, for example, with the applicationof piezoelectric sensors which, through their deformation, capture theplethysmographic wave transmitted to the skin. Based on this principle,the monitor of U.S. Pat. No. 5,131,401 requires, like the other methods,the stimulation of a peripheral motor nerve, primarily the ulnar nerve,and it comprises some cables for the stimulus electrodes and others fora sensor in the form of flexible piezoelectric sheets, which are placedon the palm of the hand and register the contraction of the muscles ofthe hand. Like the "Tof-Guard" model, it also has a microprocessorwhich, by means of a program, enables a programmed stimulation andvisualization of the quantified response of the neuromuscular block.

The primary drawback presented by these monitors, except for the lastone, is that they require the stimulation of a peripheral motor nerve,specifically the ulnar nerve, and the placement of the sensor on thehand or thumb. They likewise require the use of two electrodes forseparate stimulation of the sensor element of the response, whichincreases the risk of a detachment of the electrodes or of the sensor.

Owing to this, the placement of the electrodes may be awkward and acertain immobilization of the limb is necessary, limiting the placementin other positions. On the other hand, this type of apparatus might bemore sensitive to certain interference or involuntary movements of thepatient.

With respect to the control of the neuromuscular block, there arevarious works based on pharmacokinetic models and short-circuit models,such as those described in individual articles of medical journals:

"Quantitative assessment of residual antidepolarizing block (Partil)"Ali H. H. et al., Br J Anaesthesia 1971 vol. 43 pp. 473-477.

"Monitoring of neuromuscular function" Ali H. H. et al., Anesthesiology1976 vol. 45 pp. 216-249.

"A microcomputer based controller for neuromuscular block duringsurgery" Ritchie G. et al. Ann Biomed Eng 1985 vol. 13 pp. 3-15.

"Microcomputer based muscle relaxation monitor and controller forclinical use" Bradlow H. S. et al. Med Biol Eng Comput 1985, vol 23 pp.547-555.

"Online parameter estimation and control of D-Tubocurarine-inducedmuscle relaxation." Rametti L. B. et al., Med Biol Eng Comput 1985 vol.23 pp. 556-564.

"Online control of Atracurium induced muscle relaxation" Bradlow H. S.et al, J Biomed Eng 1986 vol. 8 pp. 772-775.

"Computer-Controlled Muscle Paralysis with atracurium in the Sheep" D.G. Lampard et al, Anesthesia and Intensive Care, vol. 41 (1986) pp.316-320.

"Clinical automatic control of neuromuscular blockade" Asbury A. J. etal, Anaesthesia 1986 vol. 41 pp. 316-320.

"Infusion of vecuronium controlled by a closed-loop system" Br J Anaesth1986 vol. 58 pp. 1100-1103.

"Closed-loop administration of Atracurium" N. R. Webster et al,Anesthesia vol. 42 (1987) pp. 1085-1091.

"A model-based self-adjusting two-phase controller forvecuronium-induced muscle relaxation during anaesthesia" Jalkist R. R.,IEEE Transac Biomed Eng 1987 vol. 34 pp. 583-594.

"Closed-loop infusion of atracurium with four different anesthetictechniques" O'Hara D. A. et al, Anesthesiology 1991 vol 74 pp. 258-263.

These articles describe instances of control of the muscle relaxation bymeans of computers with pharmacokinetic models, through the previouslymentioned sensors, or with closed-circuit systems.

There are correct approximations in all the instances, but even so theyare still experimental and not very safe models, which owing primarilyto the-need to stimulate a peripheral nerve are impractical andcomplicated in use, whether because of the type of transducer used orbecause of the pharmacokinetic model, which requires much data entry orvery sophisticated computers.

DESCRIPTION OF THE INVENTION

The aforesaid drawbacks can be eliminated with the method and apparatusof the invention.

The method for monitoring and/or controlling the neuromuscular blockwhich is the subject of the invention is characterized by the fact thatthe nerve stimulation is done on the skin covering the muscle or muscleson which the detection of the response to said stimulation is performed,that is, without having to stimulate any peripheral nerve.

Thanks to this method, it is not necessary to stimulate the peripheralnerve and the stimulator-detector device can be placed on the upper orlower limb, depending on the type of surgery being performed, withouthaving to confine the stimulation to the ulnar nerve.

Optionally, the method of the invention also comprises the automaticcontrol of the supply of the muscle relaxant drug on the basis of adetection of the muscle response.

The invention also pertains to an apparatus for the monitoring and/orcontrolling of the neuromuscular block, which comprises means for theapplication of the nerve stimulation, means for the detection of theresponse to the stimulation, and means for monitoring the neuromuscularblock, and it is characterized by the fact that the means for the nervestimulation and the means for the detection of the response are arrangedin the same body.

Thanks to this arrangement in a single body, the following advantagesare achieved:

i) a single element serves to measure the arterial pressure and tomeasure the neuromuscular block, achieving a more compact and handydevice,

ii) the placement becomes easier,

iii) the independent disconnection of certain of the components isavoided,

iv) it simplifies the monitoring in the operating theater.

According to another embodiment, the apparatus of the inventioncomprises means for the application of the nerve stimulation, means forthe detection of the response to the stimulation, and means for themonitoring of the neuromuscular block, and it is characterized by thefact that it also comprises means for supply of the drug which producesthe neuromuscular block and means of control which coordinate thegeneration of the stimulus, the registration of the activity, the dataprocessing, the computation of the drug dosage and the control of themeans for supply of the drug as a function of the computed dosage.

The apparatus of the invention thus comprises three essential parts:

i) means for the nerve stimulation, comprising the stimulator and thestimulus electrodes,

ii) means for the detection of the muscle response, consisting of asensor, which can be of various types,

iii) means of monitoring and control, which can be of various types,depending on the specific embodiment of the invention, and

iv) optionally, a closed circuit for the automatic dispensing of a drug.

The apparatus of the second embodiment can also be characterized by thefact that the means for the application of the nerve stimulation and themeans for the detection of the response are arranged in a single body,whereby the advantages already described are also obtained in thisinstance.

Preferably, the apparatus is characterized by the fact that the body isa cuff of the type used for the measurement of arterial pressure,provided with means for the detection of the pressure or connected tosaid means, whose cuffincorporates means for the application of thenerve stimulation.

In this way, the electronics and the maneuvers involved in the placementof the sensor are simplified, since the same arterial pressure cuff endtransducer of the noninvasive arterial pressure monitor are used. Thisarrangement makes it possible to simplify the technique for measurementof the neuromuscular block.

Preferably, the means for the application of the nerve stimulationcomprise at least two electrodes.

Also preferably, the means for application of the nerve stimulation andthe means for the detection of the pressure are combined with the meansof monitoring through a multiconductor tube which contains on the insidean air conduit for transmitting the pressure waves and at least one pairof electrical conductors for transmission of the stimulation pulses.

In a preferred embodiment, said conductors are included in the wall ofthe multiconductor tube.

Due to the fact that there is only a single tube which transmits thepressure wave and the contraction wave and which also includes thecables with transport the stimulus, the use of the device becomesextremely simple. This solution is also more economical, since it makesuse of the cuff and the electronic circuits of the arterial pressuremonitor. The electrical system is more simple and less cumbersome.

The method of the invention also represents a great advance with respectto all of the foregoing ones, including the most modern (Tof-Guard andU.S. Pat. No. 5,131,401), since it does not require the stimulation of aperipheral motor nerve in order to register the muscle activity. Themethod of the invention is based on the stimulation of the intramuscularneural pathways and the nerve endings of the muscular motor plate by theapplication of a stimulus current to the skin directly over the musclewhose activity one desires to gauge.

Usually, the stimulus current does not exceed 50 mA and the time ofapplication should not be more than 30 ms, in order not to directlystimulate the muscle fibers, which would produce a faulty reading of theneuromuscular block.

The means of monitoring can be any of the bloodless arterial pressuremonitors existing on the market, modified by the incorporation of apulse generator for the muscle stimulation, with the possibility ofadjusting various parameters, such as the intensity of the stimulus orthe time between readings, and with the possibility of furnishingon-screen data corresponding to the muscle relaxation.

The monitors can also have LEDs of light and sound alarm signals forcases of loss of signal or contact of the electrodes (by impedance),disconnection of the sensor or any of its parts, excessively high or lowlevel of blockage with respect to the predetermined level, as well asother alarms which are common in medical devices, such as currentfaults, loss of power supply, etc.

The means of monitoring and control comprise an insulated amplifier,with filters for 50-60 Hz and high frequency to avoid interference fromthe electrical scalpel, a stimulator circuit of the type commonly usedfor nerve stimulation, capable of generating currents up to an intensityof 100 mA, a circuit to measure and control the intensity of thestimulus current, an air pump to inflate the cuff, and optionally an A/Dconverter, a memory bus and a microprocessor which, by means of aprogram in EPROM memory, controls all the functions of the device,coordinating the following closed-circuit cycle: stimulation,registration, data processing and signal processing according tostandards for assessment of the neuromuscular block (evaluation of theTOF).

BRIEF DESCRIPTION OF THE DRAWINGS

In order to better comprehend what has been set forth, drawings areincluded which describe, schematically and only as an example, notlimited hereto, the differences from the conventional methods and apractical example of realization of the stimulus-registration device, aswell as the controller apparatus of the neuromuscular block.

FIG. 1 is a graph of the muscular activity, demonstrating the validityof the apparatus of the invention;

FIG. 2 is a scheme for a conventional placement of the electrodes andthe sensor;

FIG. 3 is a scheme in perspective view of a pressure cuff, in whichcertain stimulus electrodes have been incorporated on its inner surface,with a large-scale detail of the multiconductor "tube";

FIG. 4 shows one embodiment of the apparatus of the invention; and

FIG. 5 is a flow chart of a closed circuit which controls the infusionof a muscle relaxant drug.

DESCRIPTION OF A PREFERRED EMBODIMENT

FIG. 2 shows a conventional placement of the electrodes 1, 2 and thesensor 3. In this case, the electrodes 1, 2 are arranged on the arm andthe sensor 3 is arranged on the finger. One can see in the figure thetwo cables 4, 5 corresponding to the electrodes and the cable 6corresponding to the sensor.

FIG. 3 shows the stimulator-detector device of the apparatus of theinvention. In the figure, one can see the electrodes 7, 8 arranged in apressure cuff 9. As the large-scale detail shows, the multiconductortube 10 comprises an air conduit 11 and two electrical conductors 1 2and 13. In the embodiment shown, the conductors 12 and 13 are includedin the wall of the multiconductor tube 10.

FIG. 1 shows a continuous tracing curve A which corresponds to themethod of the invention with the pressure cuff, provided with thestimulus electrodes arranged over the muscle in which the block is beingevaluated, and a continuous tracing curve B which corresponds to aconventional method, with the stimulus electrodes over the ulnar nerveand the sensor on the thumb.

In order to demonstrate the validity of the method of the invention andto ensure that the direct cutaneous stimulation over the muscle mass inwhich one wishes to evaluate the neuromuscular block does not producedirect stimulation of the muscle fibers, but instead the stimulusfollows the intramuscular nerve pathways and nerve endings of the musclemotor plate, the following test was performed: sensors were placed onthe thumb and stimulus electrodes over the ulnar nerve, following theinstructions of the previous conventional methods. Curve B was obtained.

In the same patient and at the same time, the pressure cuff with theelectrodes on its inner surface was put in place, following theinstructions of the method of the invention. Curve A was obtained.

Comparing the trend of both curves during the application of musclerelaxant drugs to anaesthetized patients, results were obtained whichvalidate the method of the invention, since curves A and B show asimilar behavior for the same method of application of the drugs.

FIG. 4 shows the different components of the apparatus of the invention:

In the first place, the stimulator-detector device 14 detailed in FIG.3, which includes the stimulus electrodes 7, 8 and the pressure cuff 9.This can be made in different sizes, depending on the size of the limbto which it is applied, it being possible to have versions for adultsand versions for children.

The device can be disposable or reusable, and it comprises the twoelectrodes 7, 8, likewise disposable or reusable, which are coupled tothe cuff and have a stimulus surface varying between 0.05 cm2 to 5 cm2for each. The electrodes 7, 8 are placed on the inner surface of thearterial pressure cuff 9, which, with the muscle contraction wavetransmitted to the skin, generates a pressure wave proportional to themuscle contraction that is transmitted through the tube to the pressuretransducer, arranged inside a conventional type of arterial pressuremonitor 15.

The stimulation electrodes 7, 8 can be situated in various ways on theinner surface of the cuff 9. The more far apart they are, the greaterthe number of nerve endings stimulated and the larger will be theresponse.

The cycle used for the measurement is as follows:

1) Inflate the cuff slightly to ensure good contact between theelectrodes and the skin (between 10 and 300 mmHg).

2) Generation and application through cutaneous electrodes of a seriesof four stimuli <50 mA and <30 me in duration at a frequency of 2 Hz,known as "TOF" ("Train of Four", the standard accepted in all methods ofevaluation of the neuromuscular block).

3) Registration of the pressure generated inside the cuff by the wavewhich is transmitted to the surface of the skin by the contractions ofthe muscle.

4) Digitization and processing of the signal, graphic representationthrough an LCD or electroluminescent screen.

FIG. 4 shows one embodiment of the apparatus of the invention. In thisfigure, one can see the stimulator-detector device 14 as represented inFIG. 3 and a conventional type of arterial pressure monitor 15.

In the lower righthand portion of the monitor dial 15 one can see theconnections 16, 17 and 18, corresponding respectively to themulticonductor tube 10, the information on oxygen saturation, and theelectrocardiogram.

In the upper righthand portion one can see a pair of control buttons,one of which 19 serves to adjust the time between two readings and theother 20 is used to adjust the intensity of the stimulus.

On the screen at left there appear two curves, the upper onecorresponding to the electrocardiogram and the lower one to the pulsesignal or plethysmogram. The bars in the lower part of the screenrepresent the responses to the muscular stimulation over time. Thescreen can also display data such as the muscular activity (Musc: 30%),heart rate (FC: 60), arterial pressure (PA: 120/70), and oxygensaturation (Sat: 98%).

The conventional monitor 15 is provided with a pulse generator for themuscle stimulation through the conductors 12, 13 (FIG. 3) and theelectrodes 7, 8.

FIG. 5 shows a flow chart of a closed circuit. The electrical stimulator21 stimulates the muscle 22. The sensor 23 provides the muscle responseto the means of control 24.

A program is used to control the data acquisition, A/D conversion, andanalysis of the data, furnishing the signals to actuate the system forsupply or infusion of the muscle relaxant 25. In this way, the infusionwill be automatic.

I claim:
 1. A method of monitoring neuromuscular block and particularlythat produced by muscle relaxant drugs used during anesthesia, themethod comprising the steps of, stimulating the skin covering the musclein which the detection of the response to the stimulation is performedand without stimulating any peripheral nerve, detecting the muscleresponse to said stimulation, and measuring said response.
 2. The methodset forth in claim 1 including the step of controlling the supply ofmuscle relaxant to the patient in relation to the detected muscleresponse.
 3. The method set forth in claim 1 wherein said method isperformed using a pressure cuff and a nerve stimulator and sensor aremounted in the cuff, comprising the further steps of applying thepressure cuff to the patient's skin at a point covering the muscle to bestimulated, pressurizing the cuff to position the electrode against theskin, and applying a stimulating signal to the electrode.
 4. The methodset forth in claim 3 including the step of sensing changes in thepressure within the cuff as an indication of muscle response.
 5. Anapparatus for monitoring neuromuscular block, particularly the blockproduced by muscle relaxant drugs during anesthesia, said apparatuscomprising a pressure cuff, first means disposed on the pressure cufffor applying nerve stimulation to the skin covering the muscle on whichdetection of the response of the stimulation is to be performed, andsecond means disposed on said pressure cuff for detecting the responseto the stimulation, and means for monitoring the neuromuscular block. 6.An apparatus for monitoring neuromuscular block, and particularly theblock produced by muscle relaxant drugs during anesthesia,said apparatusincluding a nerve stimulator constructed and arranged to apply nervestimulation to the skin covering the muscle on which the detection ofthe response to the stimulation is performed and without the necessityof stimulating any peripheral nerves, a detector constructed andarranged to detect the response to the stimulation, a monitorconstructed and arranged to monitor the neuromuscular block, a drugsupplier constructed and arranged to supply the drug which produces theneuromuscular block, and a processor programmed to coordinate thegeneration of the stimulants, to register the activity as a result ofthe stimulus, to compute the drug dosage and to control the means forsupplying the drug supplied as a function of the computed dosage.
 7. Theapparatus set forth in claims 6 and including an arterial pressuremeasurement cuff, said nerve stimulator being mounted on the pressurecuff said detector being constructed and arranged to detect the pressurewithin said cuff.
 8. The apparatus set forth in claim 7 and including abody, said means for the application of nerve stimulation and the meansfor detecting a response to the nerve stimulation are disposed on saidbody.
 9. The apparatus set forth in claims 5 or 8 wherein said body isan arterial pressure measurement cuff, said means for detecting theresponse to the stimulation comprising means for detecting the pressurewithin said cuff.
 10. The apparatus set forth in claims 5 or 8 whereinthe means for the application of nerve stimulation comprises at leasttwo electrodes.
 11. The apparatus set forth in claim 9 and including amonitor, a conduit connecting the monitor to the pressure cuff fortransmitting pressure waves, and electrical conductor means extendingthrough the conduit and coupled to the means for the application ofnerve stimulation.
 12. The apparatus set forth in claim 11 wherein theconduit has a wall, said conductors being mounted in the wall of theconduit.
 13. The apparatus set forth in claims 5 or 8 wherein the meansfor the application of nerve stimulation comprises a pressure cuffhaving at least one electrode positioned to engage the skin when thecuff is applied.
 14. The apparatus set forth in claim 13 wherein themeans for monitoring the neuromuscular block comprises means for sensingpressure changes in the cuff.
 15. The apparatus set forth in claims 6wherein said body is an arterial pressure measurement cuff, and adetector constructed and arranged to detect the pressure within saidcuff.
 16. An apparatus for monitoring neuromuscular block, particularlythe block produced by muscle relaxant drugs during anesthesia, saidapparatus comprising a body, a nerve stimulator mounted on the body forapplying nerve stimulation to the skin covering the muscle on whichdetection of the response of the stimulation is to be performed, and adetector mounted on said body for detecting the response to thestimulation, and a monitor for monitoring the neuromuscular block. 17.The apparatus set forth in claims 16 or 15 wherein the nerve stimulatorcomprises at least two electrodes.
 18. The apparatus set forth in claim15 and including a conduit connecting the monitor to the pressure cufffor transmitting pressure waves, and an electrical conductor extendingthrough the conduit and coupled to the means for the application ofnerve stimulation.